[CIS PIDD] [cis-pidd] tricho-hepato-enteric syndrome with SKIV2L

[CIS-PIDD]

Mine have had the TTC37 mutation or an unknown mutation so I am not sure it is exactly analogous.  I will say that Dr. Badens in France was extremely helpful when we started thinking about how best to manage our patients.

The SKIV2L mutations, I believe, have been associated with an interferon signature so you might think about a JAK inhibitor but I will tell you what we did for our patients.

Our patients too had infections out of proportion to what their labs would suggest.  We used immune suppression to control gut inflammation but they were still TPN dependent.  The good news was that over time, we could withdraw the immune suppression (tacrolimus) and the child (one long term survivor) was able to eat.  She remains short and has mild cognitive impairment but is a functioning (and very cute) young adult now.  She is still dependent on immunoglobulin replacement.

Her first two years were an incredible challenge in terms of fluid management and nutrition.  Her parents get a lot of credit for being such strong advocates and managers.  The child who died, died of sepsis.


Kate Sullivan, MD PhD
Wallace Chair
Chief of Allergy Immunology
ARC 1216 CHOP
3615 Civic Center Blvd.
Philadelphia, PA 19104
(p) 215-590-1697
(f) 267-426-0363



On Jun 8, 2017, at 6:31 AM, CIS-PIDD <cis-pidd at lists.clinimmsoc.org<mailto:cis-pidd at lists.clinimmsoc.org>> wrote:

Dear All

We have recently diagnosed a 6 month old baby with tricho-hepato-enteric syndrome with SKIV2L mutation. I am interested to know of any experience with these patients as the published literature on the immunological phenotype is small.

Our patient was born at term weighing 1.5kg and had been seen by the local geneticists due to IUGR. He came to our attention at 4 months of age when he presented with PJP pneumonia, requiring high frequency oscillatory ventilation. He was also found to be CMV viraemic and had rhinovirus on naso-pharyngeal aspirate at the time.

He had hepatomegaly, ascites and synthetic liver dysfunction at presentation but did not have a history of diarrhoea. His liver biopsy demonstrated fibrosis. He was treated for the PJP and also the CMV which has since resolved. His CMV PCRS remain negative.

He came to us for investigation of primary immunodeficiency in the context of PJP and CMV. He has a mild lymphopaenia, with slightly low CD4 numbers (1200, 39%) but normal naive T cell numbers and slightly low B cell numbers (400, 12.6%) which have been fairly consistent over the last couple of months.  Lymphocyte proliferation to PHA and anti-CD3 are normal. He did receive a dose of IVIG early on in his course and his immunoglobulins have trended down since. He initially had high IgM, peaking at 4.5g/L, now down to 0.88g/L. IgA has gone from 0.75g/L to 0.18g/L. IgG has gone from 8.5 to 3.5g/L over the last month with albumin in high 20s. He has not been fully vaccinated due to being unwell so we haven't yet evaluated his vaccine responses.

Published cases of THE have hypogammaglobulinaemia but I have not seen PJP described and was wondering whether anyone else has seen this? Also, any comments on the immunological progress of these children would be useful. We are happy we have excluded alternative immunological diagnoses with functional and genetic testing. His diagnosis was made on whole exome sequencing.

He has since gone on to develop significant diarrhoea with essentially no weight gain (current weight 3.7kg) and is being managed on TPN. We are monitoring immunoglobulins and will check vaccine responses. He remains on trimethoprim-sulphamethoxazole prophylaxis.

I would be interested to hear anyone else's experience and thoughts on the significance of the PJP in this condition.

Many thanks

Theresa




Dr Theresa Cole
Paediatric Immunologist Allergist
Department of Allergy & Immunology

The Royal Children's Hospital Melbourne
50 Flemington Road Parkville 3052 Victoria
T: 03 9345 5701 F:03 9345 4848
www.rch.org.au<http://www.rch.org.au/>

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